151
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Campesterol and dithymoquinone as a potent inhibitors of SARS cov-2 main proteases—promising drug candidates for targeting its novel variants

, , , , , , , , & ORCID Icon show all
Received 06 Feb 2023, Accepted 13 Sep 2023, Published online: 30 Jan 2024

References

  • Aleem, A., Akbar Samad, A. B., & Vaqar, S. (2023). Emerging variants of SARS-CoV-2 and novel therapeutics against coronavirus (COVID-19). In StatPearls. StatPearls Publishing.
  • Aqil, K., Khan, M-U-R., Aslam, A., Javeed, A., Qayyum, R., Yousaf, F., Yasmeen, F., Sohail, M. L., & Umar, S. (2018). In vitro antiviral activity of Nigella sativa against Peste des Petits Ruminants (PPR) virus. Pakistan Journal of Zoology, 50(6), 2223-2228. https://doi.org/10.17582/journal.pjz/2018.50.6.2223.2228
  • Arooj, M., Shehadi, I., Nassab, C. N., & Mohamed, A. A. (2020). Physicochemical stability study of protein–benzoic acid complexes using molecular dynamics simulations. Amino Acids, 52(9), 1353–1362. https://doi.org/10.1007/s00726-020-02897-2
  • Azhar, E. I., Hui, D. S., Memish, Z. A., Drosten, C., & Zumla, A. (2019). The middle east respiratory syndrome (MERS). Infectious Disease Clinics of North America, 33(4), 891–905. https://doi.org/10.1016/j.idc.2019.08.001
  • Baker, N. A., Sept, D., Joseph, S., Holst, M. J., & McCammon, J. A. (2001). Electrostatics of nanosystems: Application to microtubules and the ribosome. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10037–10041. https://doi.org/10.1073/pnas.181342398
  • Barakat, E. M. F., El Wakeel, L. M., & Hagag, R. S. (2013). Effects of Nigella sativa on outcome of hepatitis C in Egypt. World Journal of Gastroenterology, 19(16), 2529–2536. https://doi.org/10.3748/wjg.v19.i16.2529
  • Cannalire, R., Cerchia, C., Beccari, A. R., Di Leva, F. S., & Summa, V. (2022). Targeting SARS-CoV-2 proteases and polymerase for COVID-19 treatment: State of the art and future opportunities. Journal of Medicinal Chemistry, 65(4), 2716–2746. https://doi.org/10.1021/acs.jmedchem.0c01140
  • Celik, I., Onay-Besı̇kcı̇, A., & Ayhan-Kilcigı̇l, G. (2021). Approach to the mechanism of action of hydroxychloroquine on SARS-CoV-2: A molecular docking study. Journal of Biomolecular Structure and Dynamics, 39(15), 5792–5798. https://doi.org/10.1080/07391102.2020.1792993
  • Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X., & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet (London, England), 395(10223), 507–513. https://doi.org/10.1016/S0140-6736(20)30211-7
  • Cosconati, S., Forli, S., Perryman, A. L., Harris, R., Goodsell, D. S., & Olson, A. J. (2010). Virtual screening with AutoDock: Theory and practice. Expert Opinion on Drug Discovery, 5(6), 597–607. https://doi.org/10.1517/17460441.2010.484460
  • Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. https://doi.org/10.1038/srep42717
  • Dalli, M., Bekkouch, O., Azizi, S. E., Azghar, A., Gseyra, N., & Kim, B. (2021). Nigella sativa L. phytochemistry and pharmacological activities: A review (2019–2021). Biomolecules, 12(1), 20. https://doi.org/10.3390/biom12010020
  • Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An N⋅ log (N) method for Ewald sums in large systems. The Journal of Chemical Physics, 98(12), 10089–10092. https://doi.org/10.1063/1.464397
  • Devaux, C. A., Rolain, J. M., Colson, P., & Raoult, D. (2020). New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? International Journal of Antimicrobial Agents, 55(5), 105938. https://doi.org/10.1016/j.ijantimicag.2020.105938
  • Douangamath, A., Fearon, D., Gehrtz, P., Krojer, T., Lukacik, P., Owen, C. D., Resnick, E., Strain-Damerell, C., Aimon, A., Ábrányi-Balogh, P., Brandão-Neto, J., Carbery, A., Davison, G., Dias, A., Downes, T. D., Dunnett, L., Fairhead, M., Firth, J. D., Jones, S. P., … Walsh, M. A. (2020). Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease. Nature Communications, 11(1), 5047. https://doi.org/10.1038/s41467-020-18709-w
  • Dupont, L., Snell, L. B., Graham, C., Seow, J., Merrick, B., Lechmere, T., Maguire, T. J. A., Hallett, S. R., Pickering, S., Charalampous, T., Alcolea-Medina, A., Huettner, I., Jimenez-Guardeño, J. M., Acors, S., Almeida, N., Cox, D., Dickenson, R. E., Galao, R. P., Kouphou, N., … Doores, K. J. (2021). Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern. Nature Microbiology, 6(11), 1433–1442. https://doi.org/10.1038/s41564-021-00974-0
  • Elhady, S. S., Abdelhameed, R. F. A., Malatani, R. T., Alahdal, A. M., Bogari, H. A., Almalki, A. J., Mohammad, K. A., Ahmed, S. A., Khedr, A. I. M., & Darwish, K. M. (2021). Molecular docking and dynamics simulation study of hyrtios erectus isolated scalarane sesterterpenes as potential SARS-CoV-2 dual target inhibitors. Biology, 10(5), 389. https://doi.org/10.3390/biology10050389
  • Glättli, A., Daura, X., & van Gunsteren, W. F. (2002). Derivation of an improved simple point charge model for liquid water: SPC/A and SPC/L. The Journal of Chemical Physics, 116(22), 9811–9828. https://doi.org/10.1063/1.1476316
  • Hannan, M. A., Rahman, M. A., Sohag, A. A. M., Uddin, M. J., Dash, R., Sikder, M. H., Rahman, M. S., Timalsina, B., Munni, Y. A., Sarker, P. P., Alam, M., Mohibbullah, M., Haque, M. N., Jahan, I., Hossain, M. T., Afrin, T., Rahman, M. M., Tahjib-Ul-Arif, M., Mitra, S., … Kim, B. (2021). Black Cumin (Nigella sativa L.): A comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients, 13(6), 1784. https://doi.org/10.3390/nu13061784
  • Harvey, W. T., Carabelli, A. M., Jackson, B., Gupta, R. K., Thomson, E. C., Harrison, E. M., Ludden, C., Reeve, R., Rambaut, A., Peacock, S. J., & Robertson, D. L. (2021). SARS-CoV-2 variants, spike mutations and immune escape. Nature Reviews. Microbiology, 19(7), 409–424. https://doi.org/10.1038/s41579-021-00573-0
  • Hashemian, S. M. R., Sheida, A., Taghizadieh, M., Memar, M. Y., Hamblin, M. R., Bannazadeh Baghi, H., Sadri Nahand, J., Asemi, Z., & Mirzaei, H. (2023). Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy? Biomedicine & Pharmacotherapy, 162, 114367. https://doi.org/10.1016/j.biopha.2023.114367
  • Hess, B., Bekker, H., Berendsen, H. J. C., & Fraaije, J. G. E. M. (1997). A linear constraint solver for molecular simulations. Journal of Computational Chemistry, 18(12), 1463–1472. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.3.CO;2-L
  • Hoffmann, M., Krüger, N., Schulz, S., Cossmann, A., Rocha, C., Kempf, A., Nehlmeier, I., Graichen, L., Moldenhauer, A.-S., Winkler, M. S., Lier, M., Dopfer-Jablonka, A., Jäck, H.-M., Behrens, G. M. N., & Pöhlmann, S. (2022). The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic. Cell, 185(3), 447–456.e11. https://doi.org/10.1016/j.cell.2021.12.032
  • Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Li, X., Zhang, L., Peng, C., Duan, Y., Yu, J., Wang, L., Yang, K., Liu, F., Jiang, R., Yang, X., You, T., Liu, X., … Yang, H. (2020). Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 582(7811), 289–293. https://doi.org/10.1038/s41586-020-2223-y
  • Khan, A. U., Tipu, M. Y., Shafee, M., Khan, N. U., Tariq, M. M., Kiani, M. R., & Shah, S. I. A. (2018a). In-ovo antiviral effect of Nigella sativa extract against Newcastle Disease Virus in experimentally infected chicken embryonated eggs. Pakistan Veterinary Journal, 38(04), 434–437. https://doi.org/10.29261/pakvetj/2018.075
  • Khan, S. A., Zia, K., Ashraf, S., Uddin, R., & Ul-Haq, Z. (2021). Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach. Journal of Biomolecular Structure & Dynamics, 39(7), 2607–2616. https://doi.org/10.1080/07391102.2020.1751298
  • Khan, T., Ahmad, R., Azad, I., Raza, S., Joshi, S., & Khan, A. R. (2018b). Computer-aided drug design and virtual screening of targeted combinatorial libraries of mixed-ligand transition metal complexes of 2-butanone thiosemicarbazone. Computational Biology and Chemistry, 75, 178–195. https://doi.org/10.1016/j.compbiolchem.2018.05.008
  • König, J., Müller, F., & Fromm, M. F. (2013). Transporters and drug-drug interactions: Important determinants of drug disposition and effects. Pharmacological Reviews, 65(3), 944–966. https://doi.org/10.1124/pr.113.007518
  • Kostoff, R. N., Briggs, M. B., Porter, A. L., Spandidos, D. A., & Tsatsakis, A. (2020). COVID-19 vaccine safety. International Journal of Molecular Medicine, 46(5), 1599–1602. https://doi.org/10.3892/ijmm.2020.4733
  • Kumari, R., Kumar, R., & Lynn, A. (2014). g_mmpbsa: A GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. https://doi.org/10.1021/ci500020m
  • Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23(1–3), 3–25. https://doi.org/10.1016/S0169-409X(96)00423-1
  • Liu, Y. Z., Wang, X. L., Wang, X. Y., Yu, R. L., Liu, D. Q., & Kang, C. M. (2016). De novo design of VEGFR-2 tyrosine kinase inhibitors based on a linked-fragment approach. Journal of Molecular Modeling, 22(9), 222. https://doi.org/10.1007/s00894-016-3088-8
  • Lobanov, M. Y., Bogatyreva, N. S., & Galzitskaya, O. V. (2008). Radius of gyration as an indicator of protein structure compactness. Molecular Biology, 42(4), 623–628. https://doi.org/10.1134/S0026893308040195
  • Mallapaty, S. (2020). Why does the coronavirus spread so easily between people? Nature, 579(7798), 183–183. https://doi.org/10.1038/d41586-020-00660-x
  • Maurya, S., Marimuthu, P., Singh, A., Rao, G. P., & Singh, G. (2005). Antiviral activity of essential oils and acetone extracts of medicinal plants against papaya ring spot virus. Journal of Essential Oil Bearing Plants, 8(3), 233–238. https://doi.org/10.1080/0972060X.2005.10643452
  • Montero-Odasso, M., Goens, S., Kamkar, N., Lam, R., Madden, K., Molnar, F., Speechley, M., & Saverio, S. (2020). Canadian Geriatrics Society COVID-19 recommendations for older adults–What do older adults need to know? Canadian Geriatrics Journal: CGJ, 23(1), 149–151. https://doi.org/10.5770/cgj.23.443
  • Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
  • Negre, C. F., Morzan, U. N., Hendrickson, H. P., Pal, R., Lisi, G. P., Loria, J. P., Rivalta, I., Ho, J., & Batista, V. S. (2018). Eigenvector centrality for characterization of protein allosteric pathways. Proceedings of the National Academy of Sciences of the United States of America, 115(52), E12201–E12208. https://doi.org/10.1073/pnas.1810452115
  • Oyero, O. G., Toyama, M., Mitsuhiro, N., Onifade, A. A., Hidaka, A., Okamoto, M., & Baba, M. (2016). Selective inhibition of hepatitis C virus replication by Alpha-zam, Nigella sativa seed formulation. African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM, 13(6), 144–148. https://doi.org/10.21010/ajtcam.v13i6.20
  • Pandey, P., Rane, J. S., Chatterjee, A., Kumar, A., Khan, R., Prakash, A., & Ray, S. (2021). Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: An in-silico study for drug development. Journal of Biomolecular Structure & Dynamics, 39(16), 6306–6316. https://doi.org/10.1080/07391102.2020.1796811
  • Parrinello, M., & Rahman, A. (1981). Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics, 52(12), 7182–7190. https://doi.org/10.1063/1.328693
  • Paudel, K. R., Patel, V., Vishwas, S., Gupta, S., Sharma, S., Chan, Y., Jha, N. K., Shrestha, J., Imran, M., Panth, N., Shukla, S. D., Jha, S. K., Devkota, H. P., Warkiani, M. E., Singh, S. K., Ali, M. K., Gupta, G., Chellappan, D. K., Hansbro, P. M., & Dua, K. (2022). Nutraceuticals and COVID-19: A mechanistic approach toward attenuating the disease complications. Journal of Food Biochemistry, 46(12), e14445. https://doi.org/10.1111/jfbc.14445
  • Pillaiyar, T., Manickam, M., Namasivayam, V., Hayashi, Y., & Jung, S. H. (2016). An overview of severe acute respiratory syndrome–coronavirus (SARS-CoV) 3CL protease inhibitors: Peptidomimetics and small molecule chemotherapy. Journal of Medicinal Chemistry, 59(14), 6595–6628. https://doi.org/10.1021/acs.jmedchem.5b01461
  • Price, D. J., & Brooks, C. L. III, (2004). A modified TIP3P water potential for simulation with Ewald summation. The Journal of Chemical Physics, 121(20), 10096–10103. https://doi.org/10.1063/1.1808117
  • Roy, R., Sk, M. F., Jonniya, N. A., Poddar, S., & Kar, P. (2022). Finding potent inhibitors against SARS-CoV-2 main protease through virtual screening, ADMET, and molecular dynamics simulation studies. Journal of Biomolecular Structure & Dynamics, 40(14), 6556–6568. https://doi.org/10.1080/07391102.2021.1897680
  • Sahu, K. K., Mishra, A. K., & Lal, A. (2020). Comprehensive update on current outbreak of novel coronavirus infection (2019-nCoV). Annals of Translational Medicine, 8(6), 393–393. https://doi.org/10.21037/atm.2020.02.92
  • Salem, M. L., & Hossain, M. S. (2000). Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. International Journal of Immunopharmacology, 22(9), 729–740. https://doi.org/10.1016/s0192-0561(00)00036-9
  • Schuhmacher, A., Gassmann, O., & Hinder, M. (2016). Changing R&D models in research-based pharmaceutical companies. Journal of Translational Medicine, 14(1), 105. https://doi.org/10.1186/s12967-016-0838-4
  • Shivanika C, Deepak Kumar S., Ragunathan, V., Tiwari, P., Sumitha A., & Brindha Devi P. (2020). Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. Journal of Biomolecular Structure & Dynamics, 40(2), 585–611. https://doi.org/10.1080/07391102.2020.1815584
  • Silveira, D., Prieto-Garcia, J. M., Boylan, F., Estrada, O., Fonseca-Bazzo, Y. M., Jamal, C. M., Magalhães, P. O., Pereira, E. O., Tomczyk, M., & Heinrich, M. (2020). COVID-19: Is there evidence for the use of herbal medicines as adjuvant symptomatic therapy? Frontiers in Pharmacology, 11, 581840. https://doi.org/10.3389/fphar.2020.581840
  • Stillhart, C., Vučićević, K., Augustijns, P., Basit, A. W., Batchelor, H., Flanagan, T. R., Gesquiere, I., Greupink, R., Keszthelyi, D., Koskinen, M., Madla, C. M., Matthys, C., Miljuš, G., Mooij, M. G., Parrott, N., Ungell, A.-L., de Wildt, S. N., Orlu, M., Klein, S., & Müllertz, A. (2020). Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences, 147, 105280. https://doi.org/10.1016/j.ejps.2020.105280
  • Subedi, L., Tchen, S., Gaire, B. P., Hu, B., & Hu, K. (2021). Adjunctive nutraceutical therapies for COVID-19. International Journal of Molecular Sciences, 22(4), 1963. https://doi.org/10.3390/ijms22041963
  • Tabassum, H., Ahmad, A., & Ahmad, I. Z. (2018). Nigella sativa L. and its bioactive constituents as hepatoprotectant: A review. Current Pharmaceutical Biotechnology, 19(1), 43–67. https://doi.org/10.2174/1389201019666180427110007
  • Taofeek, O. (2020). Molecular docking and admet analyses of photochemicals from Nigella sativa (blackseed), Trigonella foenum-graecum (Fenugreek) and Anona muricata (Soursop) on SARS-CoV-2 target. ScienceOpen Preprints.
  • Teijaro, J. R., & Farber, D. L. (2021). COVID-19 vaccines: Modes of immune activation and future challenges. Nature Reviews. Immunology, 21(4), 195–197. https://doi.org/10.1038/s41577-021-00526-x
  • Trivedi, A., Sharma, S., & Ashtey, B. (2020). Investigational treatments for COVID-19. The Pharmaceutical Journal, 304, 10–1211.
  • Ul Qamar, M. T., Alqahtani, S. M., Alamri, M. A., & Chen, L. L. (2020). Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. Journal of Pharmaceutical Analysis, 10(4), 313–319. https://doi.org/10.1016/j.jpha.2020.03.009
  • Ullrich, S., & Nitsche, C. (2020). The SARS-CoV-2 main protease as drug target. Bioorganic & Medicinal Chemistry Letters, 30(17), 127377. https://doi.org/10.1016/j.bmcl.2020.127377
  • Ullrich, S., Ekanayake, K. B., Otting, G., & Nitsche, C. (2022). Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir. Bioorganic & Medicinal Chemistry Letters, 62, 128629. https://doi.org/10.1016/j.bmcl.2022.128629
  • Vamathevan, J., Clark, D., Czodrowski, P., Dunham, I., Ferran, E., Lee, G., Li, B., Madabhushi, A., Shah, P., Spitzer, M., & Zhao, S. (2019). Applications of machine learning in drug discovery and development. Nature Reviews. Drug Discovery, 18(6), 463–477. https://doi.org/10.1038/s41573-019-0024-5
  • Yang, X., Xing, X., Liu, Y., & Zheng, Y. (2022). Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking. Frontiers in Pharmacology, 13, 962863. https://doi.org/10.3389/fphar.2022.962863
  • Yimer, E. M., Tuem, K. B., Karim, A., Ur-Rehman, N., & Anwar, F. (2019). Nigella sativa L. (Black Cumin): A promising natural remedy for wide range of illnesses. Evidence-Based Complementary and Alternative Medicine: ECAM, 2019, 1528635–1528616. https://doi.org/10.1155/2019/1528635
  • Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., Chen, H.-D., Chen, J., Luo, Y., Guo, H., Jiang, R.-D., Liu, M.-Q., Chen, Y., Shen, X.-R., Wang, X., … Shi, Z.-L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273. https://doi.org/10.1038/s41586-020-2012-7
  • Zoete, V., Cuendet, M. A., Grosdidier, A., & Michielin, O. (2011). SwissParam: A fast force field generation tool for small organic molecules. Journal of Computational Chemistry, 32(11), 2359–2368. https://doi.org/10.1002/jcc.21816

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.